Minimally Invasive Medical Procedures Utilizing Adhesion Property of Multifunctional Nanoparticles

Abstract

Minimally invasive procedures are replacing a variety of open surgeries as medical technologies advance. Thanks to the limited incision technique, many patients have been able to avoid suffering from inflammation, complications, and long recovery time. Highly sensitive imaging modalities and probes can help clinicians to identify the operation site, while tissue adhesives and sealants can promote wound closure. The cell-based therapy is considered as an alternative to surgery or organ transplantation, in which the cells are labeled with imaging probes to enable tracking and visualization of their therapeutic function. Nanoparticles are the ideal candidates for imaging probes that offer high contrast enhancement and biocompatibility. Modifying the surface of nanoparticles to enhance their adhesion to cells and biological tissues allows efficient cell labeling and closure of internal wound for therapeutic purposes. Following the Introduction chapter, Chapter 2 describes the development of multifunctional adhesives for minimally invasive procedures. By modifying their surface with silica, tantalum oxide nanoparticles can strongly adhere to biological tissues and provide contrast enhancement effects for real-time imaging modalities including X-ray fluoroscopy, X-ray computed tomography, ultrasonography, and fluorescence imaging. The thin silica coating allows the tantalum oxide nanoparticles to be dispersed stably and to adhere to substrates with a force that is comparable to clinically employed cyanoacrylate-based adhesives. Moreover, these nanoparticles overcome the limitations of cyanoacrylate such as cytotoxicity and induction of inflammation, and are thus more suitable for intracorporeal use in minimally invasive procedures. Real-time image-guided procedures, immediate sealing of puncture wounds in liver and marking of tumor, are demonstrated using surface-modified tantalum oxide nanoparticles in animal experiments. In Chapter 3, I present a simple method for efficient labeling of therapeutic cells with multifunctional nanoparticles. Disulfide bonds in cell membrane proteins are reduced to active thiol groups, and the mesoporous silica nanoparticles (MSN) with maleimide group are used to coat mammalian cells via chemical conjugation. The fluorophore-labeled mesoporous silica nanoparticles allow tracking of the coated cells and their visualization were done by intra-vital microscopy. Drug molecules can be loaded into the mesoporous silica nanoparticles for local delivery through cell implantation. Furthermore, the activities of injected cells can be enhanced via conjugation of immunosuppressant-loaded MSNs and polymers to overcome innate immune rejection.